MicroRNA-330-5p promotes the development of osteosarcoma by regulating SPRY2

Eur Rev Med Pharmacol Sci. 2019 Oct;23(20):8761-8770. doi: 10.26355/eurrev_201910_19270.


Objective: MicroRNA is an endogenous, non-coding small RNA that has a significant role in regulating organisms and pathology. Previous studies have demonstrated that microRNA-330-5p was a cancer-promoting gene. However, the role of microRNA-330-5p in osteosarcoma (OS) has not been reported. The aim of this work was to explore the characteristics of microRNA-330-5p expression in OS, and to further study its expression in OS and its relationship with clinicopathological parameters and prognosis.

Patients and methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to investigate the expression of microRNA-330-5p in 48 pairs of OS tissues and paracancer tissues, and to analyze the relationship between the expression of microRNA-330-5p and OS clinical indicators and patient prognosis. Meanwhile, qRT-PCR was performed to verify the microRNA-330-5p expression in OS cells. In addition, the microRNA-330-5p knockdown expression model was constructed using lentivirus in OS cell lines U2OS and MG63. The effects of microRNA-330-5p on the biological function of OS cells were analyzed by Cell Counting Kit-8 (CCK-8) and transwell experiments. The potential mechanism was explored by Western blot.

Results: In this paper, qRT-PCR results showed that the expression of microRNA-330-5p in OS was higher than that in paracancer tissues, and the difference was statistically significant. Compared with microRNA-330-5p low expression group, patients with high expression of microRNA -330-5p had a higher prevalence of distant metastasis and a lower overall survival rate. In vitro experiment showed that the proliferation, invasion and metastasis abilities of the cells in the microRNA-330-5p silencing group were markedly decreased compared with the negative control group (NC group). Western blot results demonstrated that microRNA-330-5p inhibitor can activate SPRY2 and regulate the expression of key proteins, such as p-Smad2, p-Smad3, TGF-β1, MMP9 and Vimentin in the TGF-β1/Smad signaling pathway. It was found that there was a mutual regulation between microRNA-330-5p and SPRY2, which promoted the malignant progression of OS.

Conclusions: The expression of microRNA-330-5p was markedly increased in OS, which was associated with distant metastasis and poor prognosis. Furthermore, we found that microRNA-330-5p may promote the vicious progression of OS by inter-modulating SPRY2 and the TGF-β1/Smad signaling pathways.

MeSH terms

  • Adolescent
  • Adult
  • Antagomirs / metabolism
  • Bone Neoplasms / genetics
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Child
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kaplan-Meier Estimate
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Osteosarcoma / genetics
  • Osteosarcoma / mortality
  • Osteosarcoma / pathology*
  • Prognosis
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Up-Regulation
  • Young Adult


  • Antagomirs
  • Intracellular Signaling Peptides and Proteins
  • MIRN330 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • RNA, Small Interfering
  • SPRY2 protein, human